FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma

BACKGROUND: This research aimed to investigate the roles of fanconi anemia complementation group D2 (FANCD2) on the regulation of ferroptosis in osteosarcoma progression. METHODS: The function of FANCD2 on cell viability, invasion, migration, and tumor growth were explored. FANCD2 and pathway-related genes were determined by western blot. Ferroptosis-associated markers were determined, including lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe(2+)), and ferroptosis-related genes. RESULTS: FANCD2 expression was increased in osteosarcoma cells. FANCD2 knockdown reduced cell viability, invasion, and migration of osteosarcoma cells. FANCD2 knockdown regulated ferroptosis-related gene expression, and distinctly increased the levels of LIP, Fe(2+), and lipid peroxidation, and these effects were reversed by a ferroptosis inhibitor Fer-1. In addition, JAK2 and STAT3 expression were reduced by silencing of FANCD2, and STAT3 activator (colivelin) distinctly reversed tumor suppressor effects of FANCD2 silencing on osteosarcoma development. CONCLUSION: These findings suggested that FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis. These findings may provide novel therapeutic ideas for clinical treatment of osteosarcoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10626-7.